In Vitro and In Vivo Exposure-Effect Relationship of Liposomal Amphotericin B against Aspergillus fumigatus
In vitro pharmacokinetic/pharmacodynamic data of liposomal amphotericin B (L-AMB) were compared with animal data from neutropenic and nonneutropenic models of azole-susceptible and azole-resistant invasive aspergillosis. L-AMB was equally effective. The in vitro fCmax (maximum concentration of free drug)/MIC ratio associated with 50% of maximal activity was 0.31 (0.29 to 0.33), similar to that in neutropenic but not nonneutropenic mice (0.11 [0.06 to 0.20]). Simulation analysis indicated that standard L-AMB doses (1 to 3 mg/kg) are adequate for nonneutropenic patients, but higher doses (7.5 to 10 mg/kg) may be required for neutropenic patients for Aspergillus fumigatus isolates with MICs of 0.5 to 1 mg/liter.
|Persistent URL||dx.doi.org/10.1128/aac.02673-18, hdl.handle.net/1765/117134|
|Journal||Antimicrobial Agents and Chemotherapy|
Siopi, M, Mouton, J.W, Pournaras, S., & Meletiadis, J. (2019). In Vitro and In Vivo Exposure-Effect Relationship of Liposomal Amphotericin B against Aspergillus fumigatus. Antimicrobial Agents and Chemotherapy, 63(6). doi:10.1128/aac.02673-18